Abstract <p>Impaired healing of skin wounds can lead to fibrotic changes, which in turn result in a violation of the mechanical properties of the tissue. The YAP signaling is actively involved in the regeneration process, which makes it possible to use this protein as a target for therapy. The investigation is focused on the potential of utilizing a suspension of primary keratinocytes (KC) and human dermal papilla (DP) cells to stimulate scar-free regeneration of human skin. The effect was then compared with that of the YAP inhibitor verteporfin (VP). The results of the study indicate the important role of YAP in the regenerative process, since its activation was associated with the formation of a fibrotic phenotype in the skin, while pronounced inhibition of the signaling led to impaired regeneration and the inability to restore normal tissue morphology. The findings demonstrate that the suspension of KC + DP cells contributes to the inhibition of YAP activity, leading to a decrease in the expression of extracellular matrix (ECM) by scar fibroblasts in vitro. The injection of cell suspension in the in vivo model into the dermis of xenografted human skin also led to a decrease in activity of the YAP, but did not cause its complete suppression, which contributed to the approximation of skin morphology to a normal state. Concurrently, the expression of ECM elements remained unchanged, while inflammatory changes exhibited a decrease in intensity. Furthermore, the epidermis underwent a process of restoration, and graft vascularization demonstrated a marked improvement. The study indicates the potential of using KC + DP cells to stimulate normal skin regeneration by regulating the activity of the YAP signaling.</p>